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Major new research shows how psychotherapy can help those struggling with antidepressant-resistant depression: more detail

I wrote an initial post yesterday on the very interesting recent Lancet paper "Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: Results of the CoBalT randomised controlled trial".  In today's post I want to give a little more context to this trial and a bit more detail about the patients treated and the treatment used.

In yesterday's post I mentioned the earlier mixed results reported when augmenting antidepressant treatment with CBASP, a form of psychotherapy which emphasises behavioural and interpersonal factors more than standard CBT does.  Of course the well known STAR*D set of trials also explored how best to respond to non-response to antidepressants.  As the dedicated "Sequenced Treatment Alternatives to Relieve Depression (STAR*D) website" highlights, this was "the largest and longest study ever conducted to evaluate depression treatment."  The memorably named paper "The STAR*D trial: The 300 lb gorilla is in the room, but does it block all the light?" commented "It cost US tax payers $35 million and the results were announced on the front page of the Washington Post - so what did the STAR*D trial tell us about how to help people presenting with depression? ... STAR*D is a large and complicated trial and like most large and complicated trials it is hard to draw clear conclusions from it. It is a trial of pharmacological treatments in those people who find drug treatments acceptable ... it provides some information about what happens to people who start on an antidepressant and provides some information about potential (but by no means all) next-step strategies. The STAR*D trial may be the 300 lb gorilla of clinical trials but disappointingly it only sheds a little light on how to manage depression in clinical practice."  The authors of last week's Lancet paper write "STAR*D and other studies answered a different question than that posed in CoBalT. They provide evidence for alternative treatment approaches to the management of individuals who do not respond to antidepressants, rather than examining the effectiveness of augmenting antidepressant medication with CBT as a next-step option."

So what were relevant underlying details of the CoBalT study?  The first point I would like to make is that the patients involved were quite a challenging group.  Although the entry criterion was simply that they were people suffering from depression who hadn't adequately responded to six weeks on an antidepressant (they still had a score of at least 14 on the (BDI) Beck Depression Inventory).  In fact many were suffering from "severe and chronic depression often associated with psychological or physical comorbidities, or both."  In the group who had added CBT, 89% had been on their antidepressant for over six months, and 67% for over a year.  75% had been depressed for more than a year, and 58% for over two years.  81% had suffered at least two previous episodes of depression, and 50% had suffered from more than five previous episodes.  68% had a family history of depression.  90% had a BDI score of at least 20, with 56% scoring in the 30's or above - overall the initial mean BDI was 31.8.  These people are a challenging group to help.

The second point I want to make is about the CBT itself.  "Participants in the intervention group received 12 sessions of individual CBT (each lasting 50-60 min), with (up to) a further six sessions when judged to be clinically appropriate by the therapist (maximum of 18 sessions) in addition to usual care from their general practitioner."  In fact "By 6 months, individuals randomised to the intervention had received a median of 11 sessions of CBT (IQR 5-13) and 62% (144) had received at least nine sessions. By 12 months, median number of sessions was 12 (6-17) and 141 participants had received at least 12 sessions."  It's noteworthy that for the comparison group, the researchers write "We placed no restrictions on the treatment options for patients randomised to be managed as usual by their general practitioner. Participants could be referred for counselling, CBT, or to secondary care, when such treatment was clinically appropriate."  CBT for the intervention group followed a standard, "classical" approach using ideas from Beck et al's 1979 book "Cognitive therapy of depression" and his daughter's 1995 "Cognitive therapy: basics & beyond".  When appropriate, adaptations were made to address treatment resistance - using Moore & Garland's 2003 "Cognitive therapy for chronic and persistent depression".  Further treatment description stated "Therapists were flexible in responding to problems raised by the patient (eg, by targeting symptoms of anxiety with appropriate cognitive behavioural models, when these were deemed important). Emphasis was also given to formulating the psychopathology in terms of conditional beliefs. Beck's theory suggests that conditional beliefs (eg, "If I am not perfect then others will reject me") increase vulnerability to depression and delay recovery."  The intervention was delivered by "11 part-time therapists ... who were representative of those working within NHS psychological services.  Ten of the 11 therapists were female, their mean age was 39·2 years (SD 8.1), and they had practised as a therapist for a mean of 9·7 years (8·1)."  Therapists received "at least 1 day of training specific to the trial from an experienced CBT therapist and trainer and weekly supervision from skilled CBT supervisors."

And the results? "The primary outcome was BDI score at 6 months, specifically a binary variable representing response, defined as a reduction in depressive symptoms of at least 50% compared with baseline. Secondary outcomes were the BDI score as a continuous variable, remission of symptoms (BDI score of less than 10), and quality of life (assessed with the short form [SF] health survey 12) at 6 and 12 months.  Other secondary outcomes at 6 and 12 months were panic, and measures of depression (patient health questionnaire 9), and anxiety (generalised anxiety disorder assessment 7) used in psychological services."  And the headline finding was that - "Individuals in the intervention group had three-fold increased odds of response at 6 months compared with those in the usual care group."  OK, this statement (although true) maybe gives a somewhat over-inflated view of the intervention's effectiveness, however the outcomes are definitely encouraging.  46% of the added CBT group had reduced their BDI score by at least 50% compared with only 22% of the usual care.  28% of the CBT group were in remission (BDI<10) compared with only 15% of the usual care group.  This is great.  This kind of "binary variable representing response" is a widely used method of reporting intervention results.  I feel this approach can often give a bit of an over-rosy picture of a treatment's success.  Initial mean BDI was 31.8. At 6 months, mean BDI in the added CBT group was 18.9 and in the usual care group 24.5 ... a 5.6 point difference.  Very worthwhile but maybe not as startling a result presented in this way as the headline "three-fold increased odds of response" derived from the yes-or-no approach to reporting treatment outcome.

The take away message is GOOD.  As the CoBalT study authors point out "Only a third of patients with depression respond fully to antidepressant medication but little evidence exists regarding the best next-step treatment for those whose symptoms are treatment resistant."  We now know that adding a dozen or so sessions of CBT to the medication has a very good chance of helping significantly.  Hurray!  It's very probable that adding other successful psychotherapy approaches like behavioural activation, interpersonal psychotherapy & problem solving would produce similar gains.  It's also probable that we can boost response rates even further by making either or both of the pharmacotherapy and psychotherapy even more effective ... and there are additional options like adding healthy lifestyle interventions that are likely to improve outcomes further still. There is plenty that can be done to help depression sufferers who do not respond adequately to initial treatment with antidepressants, and the excellent CoBalT study adds significantly and importantly to the evidence-based options.

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